The invention relates generally to treatment of movement disorders and, more particularly, to intracranial treatment utilizing identification of an incipient movement disorder.
Movement disorders such as epilepsy and Parkinson""s disease have been estimated to affect some 1-2% of the developed world""s population and up to 10% of people in underdeveloped countries. Currently, approximately 75% of those who suffer from movement disorders are responsive in some degree to drugs. However, undesirable side effects often prevent such treatment.
In addition, drug treatment often imposes a continual effect on brain cells and other tissues commonly resulting in the perpetual presence of side effects, while the movement disorder episodes, e.g., epileptic seizures, sought to be prevented occur much less frequently. Furthermore, patients often develop such high tolerances for the drugs administered that they are no longer effective at safe dosages. Therefore, there has been a need for movement disorder suppression which avoids the use of drugs.
Electrical stimulation has been utilized to treat some movement disorders. In the treatment of epilepsy, studies have been performed in which awake patients undergoing temporal lobe surgery underwent cortical stimulation. Such stimulation of the visual and hearing areas of the brain reproducibly caused the patients to experience visual and auditory phenomena. This discovery was made possible by the identification that certain brain subregions served specific functions, such as sight, hearing, touch and movement of the extremities and proved that direct electrical stimulation of the brain regions could cause partial reproduction or suppression of the functions.
As suggested by these results, it is known that certain types of treatment of specific portions of the brain are able to suppress certain unwanted behavior which results from movement disorders. This behavior may include seizures such as those suffered by epileptics. However, the studies faced a major problem in that there was an inability to precisely electrically stimulate very small volumes of the brain.
The advent of needle-shaped penetrating depth electrodes helped to overcome this obstacle faced by electrical stimulation. Depth electrodes can be placed within the brain tissue itself, enabling optimal surface contact with elements of the brain that are targeted for stimulation. This allowed for safe, chronic electrical stimulation of very small discrete volumes of brain.
There have been attempts to provide neurocybernetic prostheses for alleviating epilepsy and related disorders. U.S. Pat. No. 4,702,254 to Zabara discloses a prosthesis which comprises a miniature electronic integrated circuit with an output which augments appropriate brain neural discharge to control convulsions or seizures. The Zabara device uses neural spectral discrimination by tuning the electrical current of the prosthesis to the electrochemical properties of a specific group of inhibitory nerves that affect the reticular system of the brain. Certain electrical parameters of the prosthesis must be selected based on the electrochemical properties of the nerves desired to be activated. The patent teaches that the optimal site for the application of the prosthesis is on the vagus nerve.
While the electrical stimulation of brain tissue has been somewhat effective in the treatment of migraines, epilepsy and other neurological problems, patients often experience diminishing returns with such treatment. Furthermore, because each patient reacts differently to electrical stimulation, substantial time must be spent to determine the specific amplitude, frequency, pulse width, stimulation duration, etc. which may result in effective treatment. In addition, such parameters often require continual adjustment in order to remain effective.
In treatment, electrical stimulation has been used with the recording and analysis of electrical changes in brain activity to predict the occurrence of epileptic seizures. The time of onset of such seizures is often predictable by neural discharge monitoring, even when the exact causal nature of precipitating dysfunction is not understood. U.S. Pat. No. 5,995,868 to Dorfmeister discloses the use of electrodes to obtain signals representative of current brain activity and a signal processor for continuous monitoring and analysis of these electrical signals in order to identify important changes or the appearance of precursors predictive of an impending change. Dorfmeister mainly discusses the quick identification of the onset of a seizure; cooling a portion of the brain in response to such identification is mentioned, but he does not discuss how such cooling could be performed.
At the time of Dorfmeister, the treatment of various disorders of and injuries to the brain utilizing the transfer of heat away from (cooling) the brain was well known in the medical arts and was often performed using the external application of cold fluids, housed chemicals involved in endothermic reactions or other refrigerants. Other methods of cooling include the external cooling of blood which is recirculated through the body.
U.S. Pat. Nos. 4,750,493 and 4,920,963 to Brader are directed to a method for cooling the extracranial area during emergency care of cardiac arrest or extreme shock in order to induce vasoconstriction and intracranial hypothermia. These inventions are implemented by a topical cold pack or watertight shroud which cannot specifically cool a targeted portion in the brain. U.S. Pat. No. 5,383,854 to Safar et al. is directed to a cardiopulmonary bypass apparatus which is able to cool the blood. This device cannot specifically cool a target portion in the brain either.
U.S. Pat. No. 6,188,930 B1 to Carson is directed to a method for heating the hypothalamus which utilizes a device for cooling the surrounding body tissues. This device is not implanted, but is used temporarily during or preceding surgery. The patent discloses cooling through the circulation of a liquid or gas coolant through a catheter. Chronic cooling of a targeted portion in the brain is not disclosed.
U.S. Pat. No. 6,090,132 to Fox is directed to a method of inducing hypothermia in a mammal. This invention applies heat to the hypothalamus in order to effect a compensatory cooling response, thereby lowering body temperature. The patent discloses the direct application of heat to the hypothalamus for a temporary cooling effect. The patent does not disclose chronic treatment using an implanted device, nor the cooling of a specific portion.
U.S. Pat. No. 5,215,086 to Terry employs a neurostimulator to selectively apply electrical therapy to treat migraines. The neurostimulator delivers pulses of electricity of a specific pulse width and amplitude to the patient""s vagus nerve in order to stimulate nerve fibers and either synchronize or desynchronize the EEG and control migraines.
U.S. Pat. Nos. 5,843,093 and 6,129,685 to Howard relate to the selective treatment of neurons within the brain with particular emphasis on the treatment of Parkinson""s through pallidotomy and on the regulation of a patient""s appetite through electrical discharges to the hypothalamus. Both of these patents disclose the inactivation of neurons through the use of a cryogenic device, though they do not teach what the cryogenic device could be or how it might be safely disposed within the brain.
Despite the Dorfmeister and Howard disclosures, it has not yet been possible, upon recognition of an incipient movement disorder, to effectively and immediately cool a localized area in the brain with an implanted device episode which can avoid undue risk or injury to the brain. An implanted device for thermal treatment of movement disorders episodes which addresses the problems of known treatments would be an important advance in the art.
It is an object of the invention to provide an implanted device for thermal treatment of movement disorders overcoming some of the problems and shortcomings of prior art devices for suppressing movement disorders.
Another object of the invention is to provide a method of suppressing movement disorder episodes in people immediately upon detection of an incipient episode.
Another object of the invention is to provide a method of suppressing movement disorder episodes through the implantation of a device which, after implantation, requires no further surgery for an extended period of time.
Another object of the invention is to provide a method of suppressing movement disorder episodes through the localized transfer of heat away from a targeted portion of the brain.
Another object of the invention is to provide a method of suppressing movement disorder episodes without the use of electrical stimulation of brain tissue.
Still another object of the invention is to provide a method of suppressing movement disorder episodes without the use of drugs.
Another object of the invention is to provide a method of suppressing movement disorder episodes which safely transfers heat from selected brain tissue without risk of damage to other brain tissue.
Another object of the invention is to provide a method of suppressing movement disorder episodes which safely transfer heat from selected brain tissue without affecting surrounding brain tissue.
Yet another object of the invention is to provide a method of suppressing movement disorder episodes which transfers heat from a selected volume of the brain in an energy efficient manner.
Still another object of the invention is to provide a method of suppressing movement disorder episodes after the detection of electrical, electrochemical, chemical, optical or blood flow changes in the brain.
How these and other objects are accomplished will become apparent from the following descriptions and drawings herein.
The implanted thermal transfer device for treatment of movement disorder episodes, and method of use thereof, are intended to prevent or suppress movement disorder episodes, such as epileptic seizures, through the transfer of heat away from a targeted portion in the brain that has been previously identified as being associated with movement disorder episodes in the patient. The invention solves the problems and overcomes the limitations of the prior art, while providing pioneering advances in the state of the art.
The preferred embodiment of the apparatus of this invention provides for the rapid transfer of heat away from (cooling of) a selected portion, or volume, in a patient""s brain upon detection of a physiological symptom of an incipient movement disorder episode. This targeted portion of the brain may be a very small, point-like volume. Such physiological symptoms may be particular to the patient, and may evolve during the patient""s lifetime. The transfer of heat automatically ceases upon the attainment of sufficient cooling at the targeted portion. Such sufficient cooling may be determined by the temperature at the targeted portion, the duration of the heat transfer which may be programmed in a controller, the subsidence of physiological symptoms or the presence of physiological evidence that the episode has been suppressed.
The preferred device comprises at least one temperature-contact positioned at a targeted portion in the brain. The temperature-contact is thermally coupled to the cold junction of a heat-transfer operator such that heat is compelled to flow from the temperature-contact into the cold junction to affect cooling at the targeted portion. The temperature-contact can be positioned adjacent to the targeted portion, or simply near the targeted portion, so that heat transfer by the temperature-contact effectively cools the targeted portion.
The preferred heat-transfer operator is a Peltier cooler or a thermal-electric cooler. Such heat-transfer operators pass electricity through junctions between dissimilar metals. The atoms of the dissimilar metals have a difference in energy levels which results in a step between energy levels at each of the metals"" junctions. As electricity is passed through the metals, the electrons of the metal with the lower energy level pass the first step as they flow to the metal with the higher energy level. In order to pass this step and continue the circuit, the electrons must absorb heat energy which causes the metal at the first junction to cool. At the opposite junction, where electrons travel from a high energy level to a low energy level they give off energy which results in an increase in temperature at that junction.
In the context of this application, Peltier cooler refers to a system wherein pairs of dissimilar materials are joined at two junctions which are separated by a substantial length. For instance, for each pair the cold junction could be positioned in the brain and the hot junction could be positioned in the abdomen. The dissimilar materials may extend to each junction forming a circuit or loop. The dissimilar materials may also be separately connected to other conductors such that the circuit or loop is comprised of a cold junction of dissimilar first and second materials, a hot junction of dissimilar first and second materials, a conductor connecting the ends of the first material and a conductor connecting the ends of the second material.
Thermal-electric cooler refers to a system wherein the cold and hot junctions are not separated by a substantial length. For instance, the cold junction of the thermal-electric cooler may be positioned on the surface of the brain and the hot junction could be positioned on a surface in substantial conformity with the external surface of the skull. While in principle a single piece of semiconducting material can be used in a thermal-electric cooler, connection of multiple semiconducting materials in series is preferred to avoid the high current requirement of the single element.
As stated above, the Peltier cooler includes at least one circuit or loop of dissimilar materials, preferably semiconducting materials, which are connected at two junctions. The Peltier cooler is preferably implanted in the patient so that its cold junction is adjacent to the temperature-contact and its hot junction is located away from the brain, preferably in the torso. The hot junction is most preferably located adjacent to, and thermally coupled to, a titanium housing which acts to dissipate heat. The Peltier cooler circuit or loop which extends between the two junctions is electrically insulated and preferably implanted such that it travels from the cold junction at the temperature-contact, out of the skull, down the neck and into the torso.
In the preferred embodiment utilizing the Peltier cooler, the temperature-contact is preferably located on the distal end of a depth-electrode type probe which is implanted in the patient""s brain. The cold junction of the Peltier cooler is connected to the temperature-contact in the brain. The Peltier circuit or loop extends out of the skull through the proximate end of the probe, down the neck and into the abdomen where the hot junction can transfer heat to another device, such as a titanium housing or other metal enclosure, or otherwise allow heat to safely dissipate into the body.
For the Peltier cooler, the preferred temperature-contact is a gold or platinum foil or collar which preferably encircles a portion of the distal end of the probe. The temperature-contact must be an extremely thermally conductive material which is harmless to the surrounding brain tissue.
In the alternative embodiment using a thermal-electric cooler, the temperature-contact is a gold or platinum foil or collar which has a surface which corresponds to the surface of the brain. The temperature-contact is preferably implanted in the patient adjacent to the skull.
The temperature-contact is connected, or thermally coupled, to the cold junction of the thermal-electric cooler. The temperature-contact is preferably located on the face of the cold-junction. A portion of the skull can be removed so that the temperature-contact can be placed adjacent to the brain and the skull with the thermal-electric cooler directly adjacent to the skull. The thermal-electric cooler can be positioned in the void created when a portion of the skull was removed such that an observer of the patient could not easily perceive the implanted device.
Whether utilizing a Peltier cooler or a thermal-electric cooler as a heat-transfer operator, the heat-transfer operator is electrically connected to an implanted power source which supplies a current through the heat-transfer operator to affect heat transfer. The power source operates efficiently by powering off the heat-transfer operator supply when heat transfer is not needed. When heat transfer is desired, the power source can be activated to supply a DC current to the heat-transfer operator which will, in turn, activate heat transfer from the targeted portion through the temperature-contact to the cold junction of the heat-transfer operator.
It is contemplated that the power source may be switched on or activated automatically or remotely by a person. The power source preferably provides power from an implanted battery which holds sufficient power so that once implanted, further operations to recharge the battery, or install a new battery, are not needed for an extended period of time, perhaps for as long as the life of the patient.
The power source is preferably implanted in the patient away from the brain, most preferably in the patient""s torso. The power source can located within a titanium housing or other metal enclosure which may provide electrical grounding.
To allow for automatic activation of the heat-transfer operator, sensing-contacts are utilized to detect a physiological symptom of an incipient movement disorder episode. The sensing-contacts are preferably positioned in the brain at a location which has been determined to be a site at which symptoms of impending movement disorder episodes may be detected and measured. The physiological symptoms detected by the sensing-contact can be electrical, electrochemical, chemical, optical or blood flow changes within the brain or other symptoms.
Such electrical and electrochemical symptoms can be changes in the patient""s EEG, changes in the patient""s intracellular EEG or the like which are recognized as precursors of episodes. These electrical and electrochemical symptoms are often related to intracellular gate changes. Such electrochemical and chemical symptoms can be the presence or change in amount of certain biogenic chemicals present near the sensing-contact, particularly neurotransmitters such as amines, amine metabolites, ascorbic acid, amino acids and neuropeptides or dopamine, glutamate, aspartate, seratonin or the receptors, metabolites, precursors, agonists, antagonists or related enzymes of such chemicals or sodium, potassium or chloride ions or nitrous oxide.
The sensing-contacts may be micro sensing-contacts which have surfaces with diameters of about 25 microns. The sensing-contacts can also be macro sensing-contacts which are cylinder type collars with lengths of about 2.5 millimeters and diameters of about 1.1 millimeters. Sensing-contacts are preferably gold or platinum though, as is recognized in the art, any conductive corrosion-resistant and non-toxic material may be used.
The sensing-contacts may be micro-circuit or nano-circuit sensors which are able to measure electrical currents generated through the circuits in response to an imposed voltage signal and/or reduction/oxidation reactions of chemical species at the circuit. Such circuits are known in the electrical arts and are produced using microlithography.
The sensing-contact may also be an optical sensor which is able to determine the concentrations of substances, chemical changes or cerebral blood flow rates. Optical sensors are preferably positioned at the tip of the depth electrode so that the exposed optical sensor projects from the electrode without increasing the diameter or thickness of the implanted device.
In the preferred embodiment utilizing the Peltier cooler the sensing-contacts are preferably located on the same probe as the temperature-contact. This construction allows for efficient implantation and removal if necessary due to unanticipated problems in the patient.
When using a Peltier cooler, the sensing-contacts are connected to sensing circuitry so that, upon detection of a physiological symptom of an incipient seizure, the sensing circuitry activates the supply of current to the heat-transfer operator and heat transfer is started, enabling the cooling of the targeted portion and suppression of the movement disorder episode. The sensing-contacts are preferably connected to the sensing circuitry through the distal end of the probe. The connection between the sensing-contacts and the sensing circuitry preferably runs alongside the Peltier cooler circuit or loop in order to minimize invasiveness.
In the preferred embodiment utilizing the thermal-electric cooler the sensing-contacts do not need to be located on a probe. Instead the sensing-contacts could be located on the face of the cold junction of the thermal-electric cooler or on the temperature contact itself. The invention also provides for the placement of the sensing-contacts on a probe of the depth-electrode or flat-electrode type. When using a depth-electrode type probe, the sensing-contacts are implanted into the brain. When using a flat-electrode type probe, the sensing-contacts are implanted beneath the skull on the surface of the brain.
When using a thermal-electric cooler, the sensing-contacts are connected to sensing circuitry so that, upon detection of a physiological symptom of an incipient seizure, the sensing circuitry activates the supply of current to the heat-transfer operator and heat transfer is started, enabling the cooling of the targeted portion and suppression of the movement disorder episode. The sensing-contacts can be connected to the sensing circuitry through the distal end of the probe, or simply around the exterior of the thermal-electric cooler if no probe is used. The connection between the sensing-contacts and the sensing circuitry preferably runs alongside the connection between the thermal-electric cooler and the power source in order to minimize invasiveness.
To provide for the automatic cessation of heat transfer in either embodiment, the sensing-contacts are able to signal the sensing circuitry to cease supply of power to the heat-transfer operator upon the achieving sufficient cooling. Sufficient cooling is achieved by the attainment of a predetermined temperature at the targeted portion, after heat transfer for a programmed period of time, after attainment of a predetermined temperature for a programmed period of time, after the subsidence of physiological symptoms or upon the sensing of physiological indications of the suppression of the movement disorder episode.
The period of time necessary for sufficient cooling may be programmed into the device, preferably into the sensing circuitry, before implantation or may be programmed by a physician, the patient or another person via telemetry or other remote means after implantation.
The temperature at the targeted portion may be determined by a thermocouple or other temperature detection means located near the targeted portion. The thermocouple or temperature detection means operates to measure the temperature of the targeted portion of the brain so that sufficient cooling may be ascertained or excessive cooling may be avoided. The thermocouple or temperature detection means is preferably located on the implanted probe or on the surface of the temperature-contact or cold junction of the thermal-electric cooler. The thermocouple or other temperature detection means is preferably connected to the sensing circuitry through the connection between the sensing-contacts and the sensing circuitry (sensing-contacts-sensing circuitry connection).
The sensing-contacts are powered by the power source through the connection between the sensing-contacts and the sensing circuitry (sensing-contact-sensing circuitry connection). The power source contains such sufficient energy that its replacement or recharging is not necessary for an extended period of time, perhaps as long as the patient""s life, but at least about 3 years. The power source does not completely power off upon the sufficient cooling of the targeted portion. Rather, the power source continues to supply power to the sensing-contacts so that the sensing-contacts are able to detect the symptoms of the next movement disorder episode. The power source can be constructed so as to have a constant power component and a variable power component. The constant power component providing power to the sensing-contacts and the variable power component supplying a DC current to the heat-transfer operator to enable heat transfer.
The power source is preferably implanted in the patient away from the brain in a less sensitive area of the body. Such areas may be in the patient""s axilla or abdomen, outside the skull, or in place of a portion of the skull which is removed. The power source is preferably enclosed in a titanium housing or other metal enclosure.
The titanium housing or metal enclosure can be used as an electrical ground for the electrical components of the device, such as the power source, sensing circuitry and heat-transfer operator. However, these electrical components may be otherwise grounded in the body. The titanium housing or metal enclosure can also be used as a heat sink or heat dissipater. The relatively large surface area of the housing and its location in a less heat-sensitive area of the body enable it to release heat efficiently.
In the embodiment of the invention utilizing manual activation of heat transfer the implantation of sensing-contacts and sensing-circuitry is not necessary. Rather, the power source can be turned on or activated by a person upon the sensing of physiological symptoms of a movement disorder episode. Because the power source does not need to supply power to sensing-contacts, the power source can be completely powered off between episodes.
The physiological symptoms are typically particular to the patient. Such symptoms can be the aura preceding an epileptic seizure. The aura is the period of time before the onset of a seizure when the patient experiences sensations or acts in a manner particular to an incipient seizure. Such sensations may be a stomach ache, photosensitivity or any other feeling which the patient recognizes as a precursor to a seizure. The patient may act in a way that others around them recognize as signaling an incipient seizure. These acts can include staring into space without reacting to the immediate surroundings or slowing down in speech or motion. In addition, an animal such as a dog may sense the incipient episode and react in a manner which is recognizable as being indicative of incipient episodes.
It is also provided that physiological symptoms on the patient""s skin may be detected by a sensor worn by the patient. Upon detection of a symptom, the sensor is able to signal an alert, either audibly, through vibration or otherwise as is known in the art. The alert notifies the patient or another person to switch on the variable power source, or otherwise activate the transfer of heat away from the targeted portion. Such a sensor can be worn by the patient, for instance, on the inside of the patient""s watchband. The sensor is preferably able to detect chemical changes on the skin""s surface.
It is provided that upon identification of physiological symptoms of a movement disorder episode, the patient or another person may manually switch on the variable power source to activate heat transfer. The switching on process may include telemetry or other remote activation systems as are known in the art.
The manual embodiment is also able to utilize automatic cessation of heat transfer. Automatic cessation occurs upon reaching sufficient cooling of the targeted area. Sufficient cooling is achieved by the attainment of a predetermined temperature at the targeted portion or after heat transfer for a programmed period of time.
Finally, it is provided that the patient or another person may turn on the variable power source, or otherwise activate the heat transfer operator without the detection of a physiological symptom. Instead, such activation may be a prophylactic measure taken before the patient performs an activity during which an occurrence of a seizure would jeopardize the patient""s safety. Such an activity may be driving a car or operating machinery. The heat transfer in such a situation would preferably occur for as long as the activity lasted to ensure that no movement disorder episodes occurred. Such prophylactic use may demand a great deal of energy and, therefore, may shorten the length of use of the power variable power source.
It is also contemplated that the heat-transfer operator may be another device or system which absorbs heat from a specific predetermined area. Such a device could include a housing containing a site for endothermic chemical reactions and connected to thermal conveyers such that the thermal conveyers transfer heat from their extremities, located at the targeted portion, to the site. Such heat transfer can be accomplished through convection of fluids or conduction. The thermal conveyer must be well-insulated to allow for effective heat transfer.